Camargo CA, Smithline HA, Malice MP, Green SA, Reiss TF. Am J Respir Crit Care Med. 2003;167:528–533
Purpose of the Study.
To determine whether the addition of intravenously administered montelukast to standard therapy for patients with acute asthma would cause rapid improvement in airflow obstruction, as well as improvement in clinically relevant outcomes such as hospitalization or prolonged or additional antiasthma therapy.
Patients, 15 to 54 years of age, who were presenting with acute asthma were screened for enrollment. Requirements included a history of asthma for ≥1 year, a history of tobacco use of <10 pack-years, and no concomitant therapy with systemic corticosteroids, leukotriene modifiers, anticholinergic agents, or long-acting β-agonist bronchodilators.
This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study with a screening period and an active study period. Two doses of intravenously administered montelukast (7 and 14 mg) or matching placebo were evaluated. Serial spirometric assessments were performed at 10, 20, 40, 60, and 120 minutes and 3 and 6 hours after intravenous study drug infusion.
A total of 201 patients were randomized, and complete data were available for analysis for 194. During the screening period, there was no difference in forced expiratory volume in 1 second responses between the 7-mg and 14-mg montelukast groups. Montelukast improved forced expiratory volume in 1 second values in the first 20 minutes after intravenous administration (mean percentage change from prerandomization baseline value: 14.8% and 3.6% for the pooled montelukast and placebo treatment groups, respectively; P = .007). This benefit was observed at 10 minutes and for 2 hours after intravenous therapy. Patients treated with montelukast tended to receive less β-agonist and to experience fewer treatment failures, compared with patients receiving placebo. The study drug and placebo were similarly tolerated, and no unexpected adverse effects were observed.
Intravenously administered montelukast, in addition to standard therapy, provided rapid benefits and was well tolerated among patients with acute asthma.
A substantial proportion of asthma exacerbations continue to require prolonged management in an emergency department setting or hospitalization. In addition to standard asthma therapies, interventions involving inhaled ipratropium, intravenously administered magnesium, and inhaled helium/oxygen mixtures have been investigated. Intravenously administered montelukast, as an adjunctive therapy for these patients, may provide added benefits with current treatment options. These results must be confirmed and, in future studies, montelukast use among pediatric patients <15 years of age should be investigated.